Alzheimer's disease Flashcards
What are symptoms of alzheimer’s?
- short term memory loss
- disorientation/confusion
- language problems - stops mid conversation
- personality changes becoming confused, fearful, anxious
- poor judgement eg with money
What normally happens to amyloid precursor proteins (APP)?
- APP cleaved by alpha secretase
- sAPPalpha released and the C83 fragments remain
- C83 digested by gamma-secretase
- products are removed
What happens to amyloid precursor proteins in alzheimer’s?
- APP cleaved by beta secretase
- sAPPbeta is released, leaving the C99 fragment
- C99 is digested by gamma secretase releasing beta-amyloid (ABeta) protein
- ABeta protein forms the toxic aggregates
What is tau protein usually for
It is a soluble protein present in axons and important for assembly and stability of microtubules
What is the tau hypothesis for alzheimer’s cause
- hyperphosphorylated tau is insoluble so self aggregates
- self aggregates form neurofibrillary tangles that are neurotoxic
- tangles result ultimately in mucrotubule instability and neurotoxic damage to neurones
What is the inflammation hypothesis for the cause of alzheimer’s
- increased release of inflammatory mediators and cytotoxic prtoeins
- increased phagocytosis
- decreased levels of neuroprotective proteins
What are examples of anticholinesterases used to treat AD
Donepezil
Rivastigmine
Galantamine
What are different types of drugs used to treat AD
- anticholinesterases
- NMDA (glutamate) receptor blocker
- gamma secretase inhibitors (failed in clinical trials)
- beta amyloid
- tau inhibitors (in clinical trials)
What is the name of an NMDA receptor blocker used in AD
Memantine - a use dependant non competitive NMDA receptor blocker with low channel affinity
What are examples of beta amyloid drugs used in AD
passive drugs: bapineuzamab which is an antibody against AP protein
Solanezumab which is an antibody against AP protein
Active drugs: vaccines in developement
